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| beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis |
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| Author(s): Guo WJ (Guo, Wenjun), Pylayeva Y (Pylayeva, Yuliya), Pepe A (Pepe, Angela), Yoshioka T (Yoshioka, Toshiaki), Muller WJ (Muller, William J.), Inghirami G (Inghirami, Giorgio), Giancotti FG (Giancotti, Filippo G.) |
| Source: CELL Volume: 126 Issue: 3 Pages: 489-502 Published: AUG 11 2006 |
| Times Cited: 97 References: 46 |
| Abstract: Amplification of the ErbB2 locus, which encodes a receptor tyrosine kinase, is common in aggressive breast tumors and correlates with poor prognosis. The mechanisms underlying ErbB2-mediated breast carcinoma progression remain incompletely defined. To examine the role of the signaling and cell-adhesion receptor beta 4 integrin during ErbB2-mediated tumorigenesis, we introduced a targeted deletion of the beta 4 signaling domain into a mouse model of ErbB2-induced mammary carcinoma. Loss of beta 4 signaling suppresses mammary tumor onset and invasive growth. Ex vivo studies indicate that beta 4 forms a complex with ErbB2 and enhances activation of the transcription factors STAT3 and c-Jun. STAT3 contributes to disruption of epithelial adhesion and polarity, while c-Jun is required for hyperproliferation. Finally, deletion of the beta 4 signaling domain enhances the efficacy of ErbB2-targeted therapy. These results indicate that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and identify beta 4 as a potential target for molecular therapy of breast cancer. |
| Document Type: Article |
| Language: English |
| Reprint Address: Giancotti, FG (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, 1275 York Ave, New York, NY 10021 USA |
Addresses:
1. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA
2. Cornell Univ, Sloan Kettering Div, Weill Grad Sch Med Sci, New York, NY 10021 USA
3. McGill Univ, Royal Victoria Hosp, Mol Oncol Grp, Montreal, PQ H3A 1A1 Canada
4. Univ Turin, Dept Pathol, I-10060 Turin, Italy
5. Univ Turin, Ctr Expt Res & Med Studies, I-10060 Turin, Italy
6. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
7. NYU, Sch Med, Inst Canc, New York, NY 10016 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 075KI |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2006.05.047 |
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